Parkinson's disease (PD) is a leading aged-related neurodegenerative disorder afflicting millions of Americans currently. Clinical diagnosis of PD relies on the analysis of symptoms and signs, limited laboratory tests, and more recently, functional neuroimaging. The considerable overlap in the clinical presentation of PD with other neurodegenerative diseases, especially in their early course, increases the difficulty of differential diagnosis amongst diseases. Indeed, this has become one of the major obstacles towards the development of new protective and restorative therapies for PD. Additionally there are no established markers that can monitor PD progression, including development of cognitive impairment. To circumvent these limitations, diagnostic and prognostic biomarkers that can provide greater selectivity and accuracy for disease diagnosis and monitor the progression of PD with high sensitivity, specificity and cost effective have been actively pursued. The proposed project is based on our recent proteomics discovery work in human brain and cerebrospinal fluid (CSF), which has led to the identification of a group of protein biomarkers unique to PD diagnosis and PD progression, respectively. While brain and CSF are ideal sources for biomarker discovery in diseases related to the central nervous system (CNS), they are less preferred diagnostic and/or prognostic materials compared to plasma or serum. In this proposal, we will apply both mass spectrometry- and immunoassay-based quantitative methods in searching and quantitatively detecting panels of biomarker unique to PD and PD progression in human plasma. Such peptide- and antibody-based approaches provide several advantages for biomarker verification/validation, including high specificity, high sensitivity and multiplexing. Successful completion of this project may eventually lead to the development of clinician/patient-friendly sensitive assays that can assist with clinical diagnosis of PD as well as monitor its progression and effects of current and future therapeutic reagents. PUBLIC HEALTH RELEVANCE: In this study, we proposed to apply both mass spectrometry- and immunoassay-based targeted quantitative approaches to detect and verify brain/CSF biomarkers associated with PD and PD progression in human plasma. We hope such effort will lead to or benefit the development of a clinicians-/patients-friendly sensitive assays that can assist with clinical diagnosis of PD as well as monitoring its progression or effects of current therapeutic reagents.